Potassium Carbonate → 1-(4-(3,4-dichlorophenyl)piperazin-1-yl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide

HRID 1473474Notes

Reaction equation

HRID 1473474 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([S:12]([NH:15][C:16]3[S:17][CH:18]=[CH:19][N:20]=3)(=[O:14])=[O:13])=[CH:9][CH:10]=2)[CH:5]=[CH:4][N:3]=1.C(=O)([O-])[O-].[K+].[K+].[Cl:27][C:28]1[CH:29]=[C:30]([N:35]2[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]2)[CH:31]=[CH:32][C:33]=1[Cl:34]>CN(C=O)C>[Cl:27][C:28]1[CH:29]=[C:30]([N:35]2[CH2:40][CH2:39][N:38]([C:2]3[C:11]4[C:6](=[CH:7][C:8]([S:12]([NH:15][C:16]5[S:17][CH:18]=[CH:19][N:20]=5)(=[O:14])=[O:13])=[CH:9][CH:10]=4)[CH:5]=[CH:4][N:3]=3)[CH2:37][CH2:36]2)[CH:31]=[CH:32][C:33]=1[Cl:34]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 936011-(3,4-Dichlorophenyl)piperazineHCID 866873831-chloro-N-(thiazol-2-yl)isoquinoline-6-sulfonamide

Product 1

HCID 866875231-(4-(3,4-dichlorophenyl)piperazin-1-yl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

1-Chloro-N-(thiazol-2-yl)isoquinoline-6-sulfonamide (from Example 73, step 2; 0.050 g, 0.153 mmol) and potassium carbonate (0.106 g, 0.767 mmol) were dissolved in DMF (1.023 ml). 1-(3,4-dichlorophenyl)piperazine (0.071 g, 0.307 mmol) was added and the reaction was stirred overnight at 120° C. The reaction was filtered through a syringe filter and purified via HPLC (Phenominex C18 column, 150×30 mm, 5 micron; gradient elution 25 to 70% MeCN:H2O with 0.1% TFA modifier). The product fractions were concentrated and passed through a SCX ion exchange column (pre-wetted with methanol). The column was flushed several times with methanol, then the product was liberated by flushing the column several times with 2.0 M ammonia in methanol. The product-containing filtrate was concentrated to afford 1-(4-(3,4-dichlorophenyl)piperazin-1-yl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm=8.40 (d, J=1.8 Hz, 1H), 8.28 (d, J=8.9 Hz, 1H), 8.23 (d, J=5.7 Hz, 1H), 7.88 (dd, J=1.9, 8.8 Hz, 1H), 7.63 (d, J=5.8 Hz, 1H), 7.44 (d, J=9.0 Hz, 1H), 7.28 (d, J=4.6 Hz, 1H), 7.22 (d, J=2.9 Hz, 1H), 7.02 (dd, J=2.8, 9.1 Hz, 1H), 6.87 (d, J=4.6 Hz, 1H), 3.46 (s, 8H). m/z (ESI) 521.1 (M+H)+.

Workup

  1. filtrationThe reaction was filtered through a syringe
  2. filtrationfilter
  3. custompurified via HPLC (Phenominex C18 column, 150×30 mm, 5 micron; gradient elution 25 to 70% MeCN:H2O with 0.1% TFA modifier)
  4. concentrationThe product fractions were concentrated
  5. customThe column was flushed several times with methanol
  6. customby flushing the column several times with 2.0 M ammonia in methanol
  7. concentrationThe product-containing filtrate was concentrated

Sources & evidence

ORD record
ord-f565e881240c45a782d315ce540ed6f8
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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